Complement C3: an emerging risk factor in cardiometabolic disease

Area of Science:

• Immunology
• Metabolic Science
• Cardiovascular Science

Background:

• Complement component 3 (C3) is central to the complement system, mediating inflammatory, immunomodulatory, and metabolic responses.
• C3 activation via classical, lectin, or alternative pathways initiates the terminal complement pathway, releasing anaphylatoxin C3a.
• C3 is increasingly recognized as a cardiometabolic risk factor, implicated in obesity, dyslipidemia, insulin resistance, and diabetes.

Purpose of the Study:

• To elucidate the role of complement C3 in metabolic disorders, vascular complications, and the coagulation system.
• To investigate the interaction between C3, diabetes, and the development of atherosclerotic and prothrombotic states.

Main Methods:

• Review of epidemiological and experimental evidence linking C3 to cardiometabolic processes.
• Analysis of C3 activation pathways and downstream signaling via C3a and C3a-desarg.
• Examination of C3's interaction with the coagulation system, including its incorporation into fibrin clots.

Main Results:

• C3 activation induces inflammatory and metabolic responses, contributing to conditions like adiposity, dyslipidemia, and insulin resistance.
• C3 plays a role in both macrovascular and microvascular complications associated with diabetes.
• Evidence suggests C3 interacts with the coagulation system, promoting a prothrombotic state, particularly in diabetes.

Conclusions:

• Complement C3 is significantly involved in metabolic, atherosclerotic, and microangiopathic processes.
• Further research into complement C3 function and activation is crucial for understanding and treating cardiometabolic disorders.
• C3 represents a potential therapeutic target for managing diabetes and its associated vascular complications.